Phase-change nanobubble, and preparation method and application thereof

A nanobubble and phase transition technology, applied in its preparation, new multifunctional imaging nano-contrast agent, phase transition nanobubble field, can solve the problem of loss of biological activity of targeting factors, poor reproducibility of preparation process, difficulty in obtaining microbubbles, etc. problems, achieving highly uniform particle size, easy large-scale preparation, and good reproducibility

Pending Publication Date: 2020-09-08
HUBEI UNIV OF SCI & TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

However, these methods have many problems in practical application, such as: it is difficult to obtain nanoscale microbubbles, the obtained microbubbles have large particle size and poor particle size uniformity, poor reproducibility of the preparation process, severe mechanical action and / or Or high temperature may cause targeting factors such as peptides, proteins, antibodies to lose biological activity, etc.

Method used

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  • Phase-change nanobubble, and preparation method and application thereof
  • Phase-change nanobubble, and preparation method and application thereof
  • Phase-change nanobubble, and preparation method and application thereof

Examples

Experimental program
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Effect test

preparation example Construction

[0038] A preparation method of phase transition nanobubbles, comprising the following steps:

[0039] (1) Chitosan-polylactic acid graft copolymer is dissolved in dichloromethane as coating material, becomes oil 1 namely O 1 phase, liquid perfluoropentane as oil 2 ie O 2 phase, mix the two phases in an ice bath to make O 2 The phase is uniformly dispersed in O 1 O 2 / O 1 Mutually;

[0040] (2) will O 2 / O 1 The phase was gradually added dropwise into the water phase under magnetic stirring in an ice bath to obtain a pre-complex emulsion O 2 / O 1 / W phase;

[0041] (3) The formed pre-double emulsion phase is subjected to ultrasonic treatment until O with uniform particle size is obtained. 2 / O 1 / W complex milk;

[0042] (4) will O 2 / O 1 / W The complex emulsion is magnetically stirred under the condition of an ice bath, solidified to form nanobubbles, and then centrifuged to obtain a precipitate and then redispersed to obtain a nanobubble aqueous dispersion loade...

Embodiment 1

[0060] (1) prepare low molecular weight chitosan

[0061] With reference to the literature method (Guo Kaihua. Hydrogen peroxide method degradation preparation process of oligomeric chitosan [J]. Silicon Valley, 2010 (19): 25+34.) get 5g chitosan in 2% acetic acid solution of 100ml, wait for shell After the polysaccharide is completely dissolved, slowly drop a certain concentration of H2O2, react at 60°C for 5 hours, adjust the pH value to neutral with 2mol / L NaoH, filter to remove impurities, and precipitate with 3-5 times the amount of absolute ethanol , precipitated low molecular weight chitosan, refrigerated for 24 hours, suction filtered, and vacuum dried.

[0062] (2) prepare chitosan-polylactic acid graft copolymer

[0063] Referring to the literature method (Liang Yanhui. The preparation and performance research of the amphiphilic chitosan-polylactic acid graft copolymer of agricultural fungicide carrier [D]. Chinese Academy of Agricultural Sciences, 2012.), take 1g l...

Embodiment 2

[0068] Nanobubble Placement Stability Test

[0069] The nanobubbles prepared in Example 1 were stored in a refrigerator at 4°C, and samples were taken at regular intervals to measure their particle size using a laser particle size analyzer to evaluate the storage stability of the nanobubbles at 4°C. For the test results, see image 3 . It can be seen from the test that the particle size and potential of the nanobubbles change very little when placed at 4°C for 2 months, indicating that the nanobubbles have good stability at 4°C.

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Abstract

The invention discloses a phase-change nanobubble, and a preparation method and application thereof. The nanobubble is prepared by taking an amphiphilic material chitosan-polylactic acid grafted copolymer as a coating material and taking perfluoropentane capable of generating liquid-gas phase transformation under the action of temperature as a bubble core filling substance by adopting an emulsifying solvent volatilization method. The prepared nanobubble is creamy yellow, and the particle size is 101.1+ / -2.7 nm. The particle size change is small in two months in vitro, and stability is good. The nanobubble can enhance the ultrasonic imaging effect under action of ultrasonic waves and can be broken by the ultrasonic waves. The chitosan-polylactic acid grafted copolymer nanobubble prepared bythe emulsifying solvent evaporation method is good in in-vitro stability, and ultrasonic imaging can be enhanced. The nanobubble can load an MRI contrast agent, so that the MRI imaging effect of tumor lesions is improved. The nanobubble can also load anti-tumor drugs for targeted therapy of tumors, is a novel multifunctional iconography nano contrast agent integrating diagnosis and treatment, andthus has a great application value.

Description

technical field [0001] The invention belongs to the technical field of medicine preparation, and specifically relates to a phase transition nanobubble, its preparation method and application. The prepared nanobubble can be used for ultrasonic imaging of tumor lesions, MRI imaging diagnosis and targeted therapy of tumors, and is a kind of diagnosis and treatment An all-in-one novel multifunctional imaging nano-contrast agent. Background technique [0002] Chitosan is a kind of alkaline polysaccharide with good biocompatibility and biodegradability. Chitosan has -OH and -NH on the main chain 2 The reactive group provides a binding site for the grafting reaction and is an excellent material for the preparation of grafted polymers. It has been widely used in the research of various drug carriers such as controlled drug release, targeting, and intelligent drug delivery. [0003] The molecular structure of polylactic acid contains a large number of ester bonds, and its hydrophi...

Claims

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Application Information

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IPC IPC(8): A61K49/00A61K49/22A61K49/12A61K49/18
CPCA61K49/0002A61K49/223A61K49/126A61K49/1806
Inventor 罗斌华王慧丽何流
Owner HUBEI UNIV OF SCI & TECH
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